Emerging regulatory role of lncRNA MALAT1 in bone homeostasis: from the β–catenin–OPG/Jagged1 signalling axis to a broader regulatory network
Year: 2026
Type: article
Abstract: In recent years, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has emerged as a candidate regulator of bone homeostasis, with reported effects on the differentiation, activity and communication of osteoblasts and osteoclasts. These effects are cell-type specific, and in some experimental models they act in opposing directions. The remodeling of bone is a highly regulated process that is crucial to the integrity of the skeleton, and when misregulated, can cause metabolic bone disease, like osteoporosis and osteoarthritis. Studies in cultured cells and in rodent models indicate that MALAT1 acts on bone remodeling in part through the β-Catenin-OPG/Jagged1 pathway, affecting both osteogenic differentiation and osteoclastogenesis. In addition to this pathway, MALAT1 also regulates mesenchymal stem cell differentiation and the bone microenvironment, thus participating in a complex network of regulation that involves several signaling cascades and gene expression programs. Recent development of high throughput sequencing and functional assays has broadened the spectrum of MALAT1's role in bone metabolism, suggesting that it participates in several signalling axes rather than acting through a single dominant mechanism. This review aims to comprehensively summarize the molecular mechanisms by which MALAT1 regulates bone homeostasis, focusing on its interactions with the β-Catenin pathway and its influence on other regulatory pathways. To help clarify these pathways, we seek to advance understanding of the pathogenesis of bone metabolic disorders and to identify candidate targets for clinical intervention. Throughout, experimentally demonstrated mechanisms are distinguished from proposed models. The evidence base summarised here is almost entirely preclinical, and MALAT1 has not yet been validated as a biomarker or therapeutic target in any clinical study.
Source: Frontiers in Medicine
Authors: Yangkai Shi, Zikang Xie
Institution: Nanjing University of Chinese Medicine
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223405290